Affiliation:
1. Laboratoire de Gastroentérologie et Nutrition
2. INSERM U526 Activation des Cellules Hématopoïétiques, IFR50, Faculté de Médecine, Université de Nice-Sophia Antipolis, 06107 Nice Cedex 2, France
Abstract
ABSTRACT
Enterohemorrhagic
Escherichia coli
(EHEC) infections are associated with the modification of tight-junction permeability and synthesis of proinflammatory cytokine interleukin-8 (IL-8). In a previous study, it was demonstrated that EHEC-induced IL-8 secretion is due to the involvement of the mitogen-activated protein kinase (MAPK), AP-1, and NF-κB pathways. In this study, we investigated the effect of the yeast
Saccharomyces boulardii
on EHEC infection in T84 cells. For this purpose, cells were (i) incubated with bacteria and yeast at the same time or (ii) incubated overnight with yeast cells that were maintained during infection or eliminated by several washes before infection. Coincubation is sufficient to maintain the transmonolayer electrical resistance (TER) of EHEC-infected cells, whereas the preincubation of cells with the yeast without elimination of the yeast during infection is necessary to significantly decrease IL-8 secretion. We thus analyzed the mechanisms of
S. boulardii
action. We showed that
S. boulardii
has no effect on EHEC growth or on EHEC adhesion. Kinetics studies revealed that EHEC-induced myosin light chain (MLC) phosphorylation precedes the decrease of TER. ML-7, an MLC kinase inhibitor, abolishes the EHEC-induced MLC phosphorylation and decrease of TER. Studies show that
S. boulardii
also abolishes EHEC-induced MLC phosphorylation. We demonstrated that the preincubation of cells with
S. boulardii
without washes before EHEC infection inhibits NF-κB DNA binding activity, phosphorylation and degradation of IκB-α, and activation of the three members of a MAPK group (extracellular signal-regulated protein kinases 1 and 2, p38, and c-jun N-terminal kinase). These findings demonstrate that
S. boulardii
exerts a preventive effect on EHEC infection by (i) interfering with one of the transduction pathways implicated in the control of tight-junction structure and (ii) decreasing IL-8 proinflammatory secretion via inhibition of the NF-κB and MAPK signaling pathways in infected T84 cells.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
133 articles.
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